Brazilian researchers identify RNA that regulates cell death
Posted: July 31, 2014 at 1:45 am
PUBLIC RELEASE DATE:
29-Jul-2014
Contact: Samuel Antenor samuel@fapesp.br 55-113-838-4381 Fundao de Amparo Pesquisa do Estado de So Paulo
Researchers from the University of So Paulo (USP) have identified an RNA known as INXS that, although containing no instructions for the production of a protein, modulates the action of an important gene in the process of apoptosis, or programmed cell death.
According to Sergio Verjovski-Almeida, professor at the USP Chemistry Institute and coordinator of a research funded by So Paulo Research Foundation (FAPESP), INXS expression is generally diminished in cancer cells, and methods that are capable of stimulating the production of this non-coding RNA can be used to treat tumors.
In experiments on mice, the USP scientists were able to effect a 10-fold reduction in the volume of subcutaneous malignant tumors by administering local injections of a plasmid a circular DNA molecule containing INXS. The findings were published in the most recent issue of the journal Nucleic Acids Research.
The group headed by Verjovski-Almeida at USP has devoted the past five years to investigating the regulatory role of so-called intronic non-protein-coding genes those found in the same region of the genome as a coding gene but on the opposite DNA strand. INXS, for example, is an RNA expressed on the opposite strand of a gene coding for a protein known as BCL-X.
"We were studying several protein-coding genes involved in cell death in search of evidence that one of them was regulated by intronic non-coding RNA. That was when we found the gene for BCL-X, which is located on chromosome 20," he explained.
The researcher explained that BCL-X is present in cells in two different forms: one that inhibits apoptosis (BCL-XL) and one that induces the process of cell death (BCL-XS). The two isoforms act on the mitochondria but in opposite ways. The BCL-XS isoform is considered a tumor suppressor because it activates protein complexes known as caspases, which are required for the activation of other genes that cause cell death.
"In a healthy cell, there is a balance between the two BCL-X isoforms. Normally, there is already a smaller number of the pro-apoptotic form (BCL-XS). However, in comparing tumor cells to non-tumor cells, we observed that tumor cells contain even fewer of the pro-apoptotic form, as well as reduced levels of INXS. We suspect that one thing affects the other," the researcher said.
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Brazilian researchers identify RNA that regulates cell death